The oxidative cleavage of DNA by metal complexes is important in drug applications, the development of synthetic restriction enzymes, and studies of tertiary DNA structure. (S. Hecht, Acc. Chem. Res. 1986, 19, 83; S. Lippard, Acc. Chem. Res. 1978, 11, 211; J. Barton, Science 1986, 233, 727; P. Dervan, Science 1986, 232, 464; A. Burkhoff et al., Nature 1988, 331, 455; T. Tullius and B. Dombrosk., Science 1985, 230, 679).
Tris(polypyridyl) complexes of Rh(III) and Co(III) cleave DNA efficiently upon UV (&lt;350 nm) photolysis. Derivatization of one or more of the chelating ligands has shown that this cleavage can be made both stereo- and shape-selective (A. Pyle et al., J. Am. Chem. Soc. 1990, 112, 9432; A. pyle et al., J. Am. Chem. Soc. 1989, 212, 4520; J. Barton and A. Raphael, J. Am. Chem. Soc. 1984, 106, 2466). In these systems, it is primarily the photochemistry of the polypyridyl ligands that is responsible for the oxidative cleavage.
The complexes cis-Ru.sup.IV (bpy).sub.2 (py)O.sup.2+ and Ru.sup.IV (tpy)(bpy)O.sup.2+ (bpy=2,2'-bipyridine, tpy=2,2',2"-terpyridine) oxidize organic hydrocarbons and alcohols via hydride transfer to form Ru.sup.II OH.sup.+ and a carbocation (T. Meyer, J. Electrochem. Soc. 1984, 131, 221C; M. Thompson and T. Meyer, J. Am. Chem. Soc. 1982, 104, 4106), but have not been suggested for use in cleaving nucleic acids.
J. Barton, U.S. Pat. No. 4,699,978, discloses the use of ruthenium (II) complexes for labeling RNA (see col. 1 line 67 to col. 2 line 8) and the use of Cobalt (III) complexes (see col. 1 lines 55-60) for selectively nicking DNA.